Data from: Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis

Objective: To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis. Design: Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action. Results: We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation. Conclusions: We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

研究目标：开发并实施一套循证框架，从已获批上市的药物中筛选候选口服神经保护药物，用于继发性进展型多发性硬化症（secondary progressive multiple sclerosis）的临床试验。研究设计：首先对多发性硬化症（multiple sclerosis, MS）及其他4种具有共同病理特征的神经退行性疾病的口服疑似神经保护治疗的临床研究进行系统评价，随后针对上述干预措施的体内实验数据开展系统评价与荟萃分析。我们将汇总数据提交至一个国际多学科委员会，该委员会依据预先设定的标准依次评估每种药物，其中包含对其作用机制的考量。研究结果：我们初步筛选出52种候选干预措施。在审阅全部临床及临床前证据后，最终确定依布司他（ibudilast）、利鲁唑（riluzole）、阿米洛利（amiloride）、吡非尼酮（pirfenidone）、氟西汀（fluoxetine）、奥卡西平（oxcarbazepine）以及多不饱和脂肪酸类（包括亚油酸（Linoleic Acid）、硫辛酸（Lipoic acid）、Omega-3脂肪酸（Omega-3 fatty acid）、Max EPA油）作为临床评估的首选候选药物。研究结论：本研究证实了一套标准化、系统化的候选药物筛选方法，可用于药物挽救与重定位试验，且能广泛应用于各类神经退行性疾病。